The goal will be to identify and characterize serotonin (5-hydroxytryptaminne; 5-HT) receptor subtypes in the nervous system using a combination of molecular and electgrophysiological approaches. Three major techniques will be utilized. First, pharmacological characterization of 5-HT receptor subtypes will be performed using radioligand binding studies. An attempt will be made to define homogeneous populations of 5-HT receptor subtypes. Once identified, a specific pharmacologic "profile" for each receptor subtype will be determined. Guanine nucleotide sensitivity will be used to predict the relative agonist versus antagonist properties of drugs. Second, 5-HT receptor subtypes will be anatomically localized by autoradiography. A general autoradiographic screen will be performed in order to locate brain regions containing relatively dense populations of 5-HT receptor subtypes. Relative densities of all known subtypes will be quantitated by autoradiographic analysis in two specific brain regions: the hippocampus and somatosensory cortex. Third, in these two specific areas, the effect of 5-HT and related agents on neuronal activity will be determined using neurophysiological techniques. Field potential analysis will be used to determine the relative potencies of serotonergic agents on neurotransmission. Intracellular studies will focus on drug effects in the dentate gyrus of the hippocampus. This combination of molecular and electrophysiological approaches should greatly facilitate the characterization of 5-HT receptor subtypes in the central nervous system. Increased knowledge of the pharmacologic properties, regional localization and neuronal effects of 5-HT receptor subtypes should clarify the role of 5-HT in both normal and abnormal brain function.